Stereospecific protein-DNA interactions in nucleosomes and nucleosomal arrays of chromatin from primate cells (human, monkey) are studied from the point of view of identifying the structural elements in both the DNA sequences and protein components (histones, nonhistones) accounting for the phasing relationships in alphoid DNAs previously reported. The marked sequence preference of the classical, so-called nonspecific nucleases (e.g., microccocal nuclease) which introduces cleavages into primate DNA at specific positions has been investigated at the nucleotide level by Maxam-Gilbert sequencing and blotting analysis. The results of this investigation have confirmed the phasing relationships of alphoid DNA and have identified the sequence configurations of the preferred sites. The work also emphasizes the limitations of using nucleases as probes of chromatin structure and DNA-protein interactions in the nuclei of mammalian cells. Work has been initiated on the use of relatively nonspecific DNA cleavage reagents including bulky carcinogens such as N-acetyl-aminofluorene and methidium-propyl-EDTA(Fe) complexes as basic tools for studying the chromatin configurations determining DNA transcription control in human and monkey cells. Work on the KpnI family of long, interspersed repetitive sequences in primate cells has shown that the sequences are present in human genome libraries with a frequency such that each human gene could have at least one member of these long (1.2 to greater than 6 kilobases) sequence families associated with it. The sequences have been located and mapped adjacent to human betaglobin genes and actin genes. Studies of their structure and transcription by polymerase II indicate that the KpnI families in human cells are formally analogous to transposable elements previously identified in lower organisms (e.g., Drosophila, yeasts) and could similarly function in the control of gene expression in normal and cancer cells.